We have recently demonstrated that infusions of insulin and glucagon strikingly enhances survival of mice with a fulminant murine hepatitis. We plan to employ in vitro and in vivo model systems to investigate the means by which hormonal agents may influence the course of liver cell injury and repair. With these model systems, we will attempt to confirm and more clearly define the protective effects of insulin and glucagon noted in our previous studies and extend our prior observations regarding the enhancing effect of hormone treatment upon the repair process in both toxic and viral induced liver injury. We will seek out the mechanism, both cellular and molecular, through which insulin and glucagon produce the effect described. By probing experimental models, at least some of which respond dramatically to infusion of the two pancreatic hormones, we are attempting to define the physiologic mechanisms that regulate certain aspects of liver function and growth. An additional thrust involves the use of a well characterized rat primary hepatocyte monolayer culture system which is extremely sensitive to the actions of insulin, glucagon and EGF in various combinations and concentrations. With this nodel system we will probe the hormone regulation of hepatocyte DNA synthesis.